Microfluidic analytical systems have been gaining substantial interest for use in performing myriad chemical and biochemical analyses and syntheses. For example, such systems have been described for use in performing nucleic acid amplification reactions (See U.S. Pat. Nos. 5,498,392 and 5,587,128), for use in performing high throughput screening assays, e.g., in drug discovery operations (See commonly owned Published International Application No. WO 98/00231), for use in nucleic acid separations (See Published PCT Application No. WO 96/04547), and for a variety of other uses. These microfluidic systems generally combine the advantages of low volume/high throughput assay systems, with the reproducibility and ease of use of highly automated systems.
Because of the above advantages, it would generally be desirable to expand the applications for which these systems are used, as well as expand the scope of the advantages which such systems offer over conventional assay systems, e.g., faster throughput, lower volumes, etc. One area of particular interest is the performance of temperature responsive reactions, e.g., reactions that progress faster at higher temperatures, or require a substantially elevated base temperature to occur. In many cases, desirable chemical and biochemical reactions can be substantially expedited by performing the reaction at substantially elevated temperatures. However, in fluid systems, and especially aqueous fluid systems, a practical limit on the temperature of the operation generally is imposed by the boiling point of the fluid. For example, in aqueous systems, the boiling temperature of the fluid at or near 100xc2x0 C. is the effective maximum achievable temperature at ambient pressures of approximately 1 atm.
In order to perform reactions that utilize or even require temperatures that are above the boiling point for the fluid reactants, the use of pressure sealed reaction vessels are typically required to elevate the boiling temperature of the fluid by increasing the ambient pressure for the reaction. Unfortunately, in many reaction systems, the use of such sealed containers is impracticable. For example, in microfluidic systems, the extremely small scale of the fluid carrying elements of the system and thus the fluid volumes used, as well as the nature of the fluid transport systems employed, typically prohibit the use of pressure sealed reaction containers.
Additional concerns are raised in microfluidic systems where the presence of a bubble or bubbles, e.g., from inadvertent boiling of fluids within the system, can have extremely detrimental effects on the system by significantly fouling or plugging channels of the system. Such fouling can inhibit or completely block the ability to move fluids through the channels of the system, as well as the ability to monitor the contents of the system, e.g., using amperometric or potentiometric means. Further, in microfluidic devices employing electrokinetic material transport systems to move materials through the microscale channels of the device, such fouling can result in a cascade effect where the blockage results in higher current densities through the remaining portions of the channel which leads to greater heating. This greater heating, in turn, leads to more bubbles within the channels from boiling of the fluids.
It would therefore be desirable to be able to perform reactions at temperature levels that are at or substantially above the boiling point of the fluids used in the reaction, while benefiting from the advantages of microfluidic systems. The present invention meets these and a variety of other needs.
The present invention is generally directed to methods and systems for performing chemical and biochemical reactions at superheated temperatures by carrying out the reactions in microscale fluidic channels. Also provided are applications of these methods and systems, as well as ancillary systems for use with these methods and systems in monitoring and controlling the performance of the methods of the invention.
In one aspect, the present invention provides methods for performing reactions at superheated temperatures, which comprise placing at least a first reactant in a microscale fluidic channel. An effective level of energy then is applied to the fluid in the microscale channel, whereby the fluid is heated to a superheated temperature without boiling the fluid within the channel.
In a related aspect, the invention also provides a method for performing a reaction at a superheated temperature, which comprises providing a substrate having at least a first microscale channel disposed therein. The substrate is in communication with an energy source that delivers the sufficient level of energy to the contents of the microscale channel to heat said contents to superheated temperatures. The first reactant then is placed into the microscale channel, and the sufficient level of energy from said energy source is applied to the microscale channel to heat the contents of the channel to superheated temperatures.
In a further aspect, the present invention also provides systems for carrying out the methods described herein. In particular, these systems comprise a microfluidic device that includes at least a first substrate having a microscale channel disposed therein, where the microscale channel has at least first and second unintersected termini. A heating system is also included to apply energy to the microscale channel to heat a fluid in the channel to superheated temperatures, without boiling the fluid in the channel. Further, a controller is also provided for maintaining the energy applied from the heating system to the microscale channel at a level sufficient to superheat contents of the microscale channel without boiling the contents of the channel.